Ecological Fitness of Vibrios and the Emergence of Pathogenic Traits

描述(由申请人提供)：众所周知，致病岛(PAI)的获取有助于环境细菌向致病生物体的转化。然而，在遗传相似的菌株中，是什么限制或促进了PAI的获得，人们仍然知之甚少。O-抗原是一种高度多样化和菌株特异性的结构，覆盖在革兰氏阴性细菌的细胞表面，已被证明在环境中的致病和生存中发挥着重要作用。我推测，PAIS和O-抗原的某些组合在特定的(微型)生境(如无脊椎动物的肠道、浮游生物、动物表面)提供了生态适应性优势，这使特定的菌株组易于向致病方向进化。弧菌是革兰氏阴性细菌；某些菌株会感染海洋动物和人类宿主。由于弧菌大量存在于海洋栖息地，这些细菌对人类和我们的国家水产养殖都构成了持续的威胁。因此，有必要检测海洋环境，因为海洋环境可能是新出现病原体的储存库，以便监测这些细菌种群并预测潜在的大流行。波尔茨实验室已经从确定的海洋栖息地中分离出数千种微小不同的弧菌。这种菌株收集是同类中最具排他性的，为研究致病性的出现提供了一种极好的手段。我的研究将利用这一收集以及从不同海洋生境分离的其他弧菌：(I)利用MLSA和系统发育方法，基于核心基因微多样性来表征弧菌的亚群；(Ii)确定在这些环境弧菌中出现Pais和毒力基因的频率。将利用生物信息学方法从已知的弧菌毒力基因座和从已发表的基因组中鉴定出的其他Ioci中开发探针；这些探针将用于使用PCR和Southern blotting技术寻找毒力遗传元件；(Iii)确定O-抗原多样性与毒力基因座共存的水平及其与特定环境的相关性。WB*区域编码有助于组装O-抗原的基因；该区域将被分离和测序，以表征这个遗传多样性的基因座。毒力基因座和WB*区的频率和组合将有助于确定某些环境是否是病原体的温床。病原体感染特定的宿主并导致疾病。这项工作的相关性是确定不同的海洋环境是否是对人类和商业水产养殖构成威胁的新病原体的储藏库。结果可能会导致对如何监测和预测细菌爆发的洞察。

DESCRIPTION (provided by applicant): It is well established that the acquisition of pathogenicity islands (PAIs) assists the transformation of environmental bacteria to disease causing organisms. Yet, it remains poorly understood what limits or promotes the acquisition of PAIs among genetically similar strains. The O-antigen is a highly diverse and strain-specific structure covering the cell surface of Gram-negative bacteria that has been shown to play important roles in both pathogenesis and survival in the environment. I hypothesize that certain combinations of PAIs and O-antigens provide ecological fitness advantages in specific (micro) habitats (e.g., invertebrate guts, plankton, animal surfaces) and that this predisposes specific groups of strains to evolve towards pathogenicity. Vibrios are Gram-negative bacteria; certain strains infect marine animal and human hosts. Because Vibrios are abundant in marine habitats, these bacteria present ongoing threats to both humans and our national aquaculture. Thus, it is necessary to detect marine environments, which may be reservoirs for emerging pathogens in order to monitor these bacterial populations and predict potential pandemics. The Polz laboratory has isolated thousands of microdiverse Vibrios from defined marine habitats. This strain collection is the most exclusive of its kind and presents an excellent means to investigate the emergence of pathogenicity. My research will utilize this collection, as well as other Vibrios isolated from different marine habitats to: (i) characterize subpopulations of Vibrios based on core gene microdiversity using MLSA and phylogenetic approaches, (ii) determine the frequency that PAIs and virulence genes occur in these environmental Vibrios. Probes will be developed from known Vibrios virulence loci and other Ioci identified from published genomes using bioinformatics methods; these probes will be used to find virulence genetic elements using PCR and Southern blotting techniques, (iii) determine at what level O-antigen diversity co-exists with virulence loci and their correlates to specific environments. The wb* region encode genes that help assemble the O-antigen; this region will be isolated and sequenced to characterize this genetically diverse locus. The frequency and combination of both virulence loci and the wb* region will help determine if certain environments are breeding ground for pathogens. Pathogens infect particular hosts and cause disease. The relevance of this work is to determine if different marine environments are reservoirs for emerging pathogens that pose threat to both humans and commercial aquaculture. Results may lead to insights on how to monitor and predict bacterial outbreaks.